The overall long-term goal of this investigation is to identify, map, and determine the mechanism of action of gene(s) responsible for susceptibility to Graves disease. Specific aims are to examine the role of candidate loci such as KM and TNFalpha in Graves diesease by case- control studies and to determine whether there is a major gene for Graves disease and if this gene is linked to any of the candidte loci by employing segregation and linkage analyses in families with Graves disease.